The three dimensional structure of human serum albumin will be determined with the use of X-ray crystallography. Crystals will be grown under conditions which are as close to physiologically normal as is possible. A physiologically reasonable concentration of fatty acid or fatty alcohol (1-3 moles fatty acid/mole albumin) will be added to the albumin before crystallization. Increased salt concentrations will be used to induce precipatation. Our first goal will be to determine a low resolution (5.5 A) structure of albumin. This will allow us to determine the general size and shape of the molecule. Moreover, by means of heavy atom labeling of the fatty acids, we will probably be able to discern at low resolution the binding loci of the fatty acid molecules which are transported by serum albumin. Ultimately, at higher resolution, chemical and structural factors effecting the fatty acid binding by albumin will become evident. Also during the initial studies we intend to attempt to bind to the crystals drugs such as one of the coumarin anticoagulants or digitalis as well as metabolites such as bilirubin or thyroxine since albumin has been shown to be important in the transport of all of these compounds.